Evidence has been accumulating that blood group antigens are modified in human epithelial tumors. This change has been observed as a deletion of normal blood group antigens (A or B determinant) in cancer tissue and their replacement by precursor blood group antigens (H or Lewis a or Lewis b). In some tumors, the appearance of a heterologous or incompatible blood group antigens (e.g. A-like antigen in B or 0 individuals) has been observed. Our knowledge of the chemical basis and immunological relation of these changes is still very fragmentary. This study proposes a systematic investigation of the chemical and immunological changes in blood group antigens as related to the type of human tumor and blood group of the individuals. The study is also directed at the possibility that blood group antigens or their modified molecules may play a role in immunity of tumors. Purification, extensive fractionation, analysis of polymorphic state of antigens, and structural determinations of each antigenic component will be carried out to compare normal epithelial tissues with those of individual tumors of different blood groups. For this method of separation and structural determination of antigens, mass spectrometry, application of high pressure gas chromatography, a new methylation analysis and of a micro-anomeric analysis by means of enzymes will be used. Since these techniques are still under development, application of these new methods to antigenic analysis is one of the aims of this proposal. This study will explain the statistical relationships existing between blood group and the incidence of human cancer, and ultimately provide a clue to control of human cancer.